A Novel Cuproptosis-Related Gene Signature Predicts Prognosis in Papillary Thyroid Carcinoma Patients

Jun Cao ¹, Shijia Zhang ^2,3, Kehui Zhou ^2,3

⁰Department of Head and Neck and Rare Oncology, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, Zhejiang 310022, China.

Combinatorial Chemistry & High Throughput Screening +

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September 10, 2024

View abstract on PubMed

Summary

Cuproptosis-related genes (CRGs) are linked to mitochondrial metabolism and thyroid cancer. A novel CRG signature effectively predicts prognosis and immunotherapy response in papillary thyroid cancer (PTC) patients.

Area Of Science

Cell death mechanisms
Mitochondrial metabolism
Cancer biology

Background

Cuproptosis, a novel cell death pathway, is regulated by protein lipoylation and linked to mitochondrial metabolism.
The clinical relevance of cuproptosis-related genes (CRGs) in thyroid cancer, particularly papillary thyroid cancer (PTC), is not well understood.
This study investigates the role of CRGs in PTC and develops a prognostic signature.

Purpose Of The Study

To explore the differential expression and genetic alterations of CRGs in papillary thyroid cancer (PTC).
To construct a CRG-based signature for predicting PTC patient prognosis.
To assess the association of the CRG signature with the tumor immune microenvironment and potential immunotherapy efficacy.

Main Methods

Utilized The Cancer Genome Atlas (TCGA) database to analyze the expression of 10 CRGs in PTC.
Constructed a CRG signature using univariate and LASSO Cox regression analyses.
Validated the signature's prognostic value and molecular associations through functional enrichment, immune infiltration analysis, an independent cohort, and qRT-PCR for CDKN2A expression.

Main Results

PTC patients were classified into high and low CRG score groups, with lower overall survival (OS) in the high CRG score group.
The CRG score demonstrated strong predictive accuracy for OS (3-year AUC: 0.872, 5-year AUC: 0.941, 8-year AUC: 0.976) and served as an independent prognostic indicator.
The CRG signature correlated with the tumor immune microenvironment, showing higher immune suppression in the high CRG score group. CDKN2A expression was validated via qRT-PCR.

Conclusions

The developed CRG signature is a powerful tool for predicting prognosis in PTC patients.
CRGs are implicated in PTC tumorigenesis and may serve as biomarkers for predicting immunotherapy response.
Further research into CRGs could enhance therapeutic strategies for PTC.

Keywords:

TCGA. Thyroid cancer cuproptosis gene signature prognosis

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